Jeffrey Bland, PhD (May 17, 2016) questions the conventional framing that obesity per se causes chronic diseases. He reviews evidence that modestly elevated BMI may not increase—and can sometimes decrease—long-term disease risk, while severe obesity (BMI >35–40) clearly increases risk. He notes 20–30% of obese people lack metabolic disturbances and uses the example of the GLP-1 agonist Saxenda to show weight loss does not uniformly restore metabolic health. Bland proposes chronic inflammation (from infection, injury, immune imbalance, gut microbiome disruption, or environmental toxins) may underlie metabolic disease and produce obesity as a phenotype, arguing researchers and clinicians should investigate inflammation rather than focus solely on weight loss.
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So I'd like to talk a moment about obesity. We all know this is a huge problem. It's one that's ever increasing globally. And there's this very, very strong concern that obesity is going to create such a health catastrophe that it will bring all of the global health care system down in the economy down with all these diseases that seem to be associated with obesity. So there is a very strong push, obviously, and I think a justifiable push to manage obesity. But now there's another rising tide of discussion about obesity. When does obesity or elevated body mass index really start to have an adverse impact upon health? And as you probably know, that story is a lot more controversial because it's being seen that maybe slightly overweight is not associated with an increased risk of disease, but actually potentially a decreased risk to certain diseases over the long term, particularly in older age. It's certainly true that this is a J curve that as you get into greater, greater states of body mass index, or you get into morbid obesity with BMI's above 35 or 40, now you certainly do have a very strong increased risk to all these diseases, diabetes, heart disease, cancers, hypertensive stroke and all those things. But in the intermediate kind of ranges of increase of BMI above what used to be considered ideal, you may actually impart in certain age groups a protective effect of, against some of these diseases. What I start seeing, however, when we start looking at this literature and looking at things like the use of saxinda for weight loss, which you know is a new drug, have been approved for weight loss. It's an injectable glp, one glucagon, like one peptide agonist, that basically stimulates insulin sensitivity and lowered inflammation and it increases the thermogenic capability of cells and increases weight loss. That drug, if you look at its impact on weight loss, is quite consistent, producing between a three and a half and a five kilograms, so something on the order of say an eight to a 12 pound weight loss over the course of three months. But it doesn't necessarily improve all the metabolic parameters that's associated with disturbed metabolism. And in fact, 20 to 30% of people that are metabolic, that are obese do not have metabolic disturbance. So it's not obesity in and of itself that causes possibly these disturbed states of metabolism that we call disease. There's something that is associated with disease that may be the real cause of these particular problems. It's not just obesity itself. Now, what else could it be? Well, the emerging thought is maybe it's chronic inflammation. Inflammation resides underneath then and the phenotype then becomes obesity. So not everybody with elevated body mass is necessarily inflamed and therefore maybe what we're looking at is the wrong thing when we just focus all of our energy on weight loss. We should be looking at why people have chronic inflammation resident regardless of their body mass index. Because across the board those are the individuals that appear to have the most consistent increased incidence of these chronic age related diseases. So I think that this construct, that obesity is the problem, may be slightly misdirected. We ought to say what underlies the appearance of obesity, and it could be the disturbances in metabolism for which obesity is a phenotype. But it's associated with chronic inflammatory conditions. Then it begs the question, what causes inflammation? Does it reside as a chronic infection? Does it reside as a chronic injury? Does it require it as an immunological imbalance that's associated with the exposure to something that the immune system is overreacting to? Is it a consequence of gut microbiome disturbances? All of these things now start to become very important questions. Or could it be the exposure to toxic chemicals that activate the immune system to then create these inflammatory states of function? So I would say keep the eyes and ears open. This construct that obesity causes diabetes, heart disease and cancer, I think is under extraordinarily new evaluation as we start to see that there are 20 to 30% of people who are obese who don't get these chronic diseases, and that people that are modestly overweight may actually have protection against some of these disorders. Keep tuned.
